Data in the literature has consistently shown that there is not only significant inherent contrast in the electrical bioimpedance of normal and neoplastic breast tissue but also that spectroscopic response can provide important functional information. Further, efforts to develop tomographic imaging systems based on electrical impedance have matured to the point where many of its basic principles and practices are well understood. Project II, Electrical Impedance Spectroscopy and Imaging (EIS), has exploited this foundation to target identification of the most promising roles for EIS imaging in the setting of clinical breast care. During the current funding period, it has completed an ambitious effort to construct, deploy and initially evaluate an ultra-fast, multi-channel, multi-frequency imaging system capable of delivering a volumetric breast exam safely, comfortably and efficiently. The system and its prior prototypes have been used in well over 100 clinical sessions in order to (i) establish exam consistency, (ii) identify normative responses in breasts without disease, (iii) explore electrical property variations due to hormonal changes during the menstrual cycle and (iv) evaluate the detection and characterization of screening abnormalities. The driving force for Project II renewal is optimization, validation and thorough evaluation of the most recently installed EIS imaging system which is, by far, the most advanced version of the instrument that is expected to improve considerably the prior encouraging results. The specific aims for continuation include (1) data acquisition and breast interface optimization of electrode density, geometry, and registration for three-dimensional, high frequency EIS breast imaging, (2) software optimization for ultrafast frame-rates, multi-tone testing, virtual current drive along with three-dimensional high frequency image reconstruction, (3) development, validation and utilization of a probe-based measurement system suitable for studies of EIS-imaged breast tissues at the time of surgical resection, and (4) participation in clinical studies conducted through the Clinical Core which target screening abnormalities recommended for biopsy, palpable masses on clinical breast exams and locally-advanced cancers receiving neoadjuvant therapy. If successful, it is expected that these aims will generate sufficient evidence to allow convincing estimates of the potential of EIS breast imaging as an alternative for differential diagnosis and pilot data in support of a role in treatment prognosis and therapy monitoring to be made which would inform decisions on the initiation of multi-center trials with the technology in the future.